'Smart' Bio-nanotubes Developed; May Help In Drug Delivery

The nanotubes are "smart" because in the future they could be designed toencapsulate and then open up to deliver a drug or gene in a particular locationin the body. The scientists found that by manipulating the electrical charges oflipid bilayer membranes and microtubules from cells, they could create open orclosed bio-nanotubes, or nanoscale capsules.The news is reported in an articleto be published August 9 issue of the Proceedings of the National Academy ofSciences. It is currently available on-line in the PNAS Early Edition. See: http://www.pnas.org/cgi/content/abstract/0502183102v1

The findings resulted from a collaboration between the laboratories of CyrusR. Safinya, professor of materials and physics and faculty member of theMolecular, Cellular, and Developmental Biology Department, and Leslie Wilson,professor of biochemistry in the Department of Molecular, Cellular andDevelopmental Biology and the Biomolecular Science and Engineering Program. Thefirst author of the article is Uri Raviv, a post-doctoral researcher inSafinya's lab and a fellow of the International Human Frontier Science ProgramOrganization. The other co-authors are: Daniel J. Needleman, formerly Safinya'sgraduate student who is now a postdoctoral fellow at Harvard Medical School;Youli Li, researcher in the Materials Research Laboratory; and Herbert P.Miller, staff research associate in the Department of Molecular, Cellular andDevelopmental Biology.

The scientists used microtubules purified from the brain tissue of a cow fortheir experiments. Microtubules are nanometer-scale hollow cylinders derivedfrom the cell cytoskeleton. In an organism, microtubules and their assembledstructures are critical components in a broad range of cell functions ---- fromproviding tracks for the transport of cargo to forming the spindle structure incell division. Their functions include the transport of neurotransmitterprecursors in neurons.

"In our paper, we report on a new paradigm for lipid self-assembly leading tonanotubule formation in mixed charged systems," said Safinya.

Raviv explained, "We looked at the interaction between microtubules ----negatively charged nanometer-scale hollow cylinders derived from cellcytoskeleton ---- and cationic (positively charged) lipid membranes. We discoveredthat, under the right conditions, spontaneous lipid protein nanotubules willform."

They used the example of water beading up or coating a car, depending onwhether or not the car has been waxed. Likewise the lipid will either bead up onthe surface of the microtubule, or flatten out and coat the whole cylindricalsurface of the microtubule, depending on the charge.

The new type of self-assembly arises because of an extreme mismatch betweenthe charge densities of microtubules and cationic lipid, explained Raviv. "Thisis a novel finding in equilibrium self-assembly," he said.

The nanotubule consisting of a three-layer wall appears to be the way thesystem compensates for this charge density mismatch, according to the authors.

"Very interestingly, we have found that controlling the degree ofovercharging of the lipid-protein nanotube enables us to switch between twostates of nanotubes," said Safinya. "With either open ends (negativeovercharged), or closed ends (positive overcharged with lipid caps), thesenanotubes could form the basis for controlled chemical and drug encapsulationand release."

The inner space of the nanotube in these experiments measures about 16nanometers in diameter. (A nanometer is a billionth of a meter.) The wholecapsule is about 40 nanometers in diameter.

Raviv explained that the chemotherapy drug Taxol is one type of drug thatcould be delivered with these nanotubes. The scientists are already using Taxolin their experiments to stabilize and lengthen the lipid-protein nanotubes.

The work was performed using state-of-the-art synchrotron x-ray scatteringtechniques at the Stanford Synchrotron Radiation Laboratory (SSRL), combinedwith sophisticated electron microscopy at UCSB. The work was funded by theNational Institutes of Health and the National Science Foundation. SSRL issupported by the U.S. Department of Energy. Raviv was also supported by theInternational Human Frontier Science Program and the European Molecular BiologyOrganization.